Dendritic cells (DCs) play a key role in the immune system, for they are the most effective antigen presenting cells for initiating primary immune responses and they have the ability to initiate T cell mediated immune responses. DCs have widespread tissue distribution and are generally present in the body at locations that are routinely exposed to foreign antigens, such as the skin, lung, gut, blood and lymphoid tissues (see Steinman, R. M., Annu. Rev. Immunol. 9:271-2996 (1991)).
Generally, DCs are either classified as immature or mature. Peripherally located immature DCs endocytose and process antigen efficiently, but express low levels of costimulatory molecules CD40, CD80 and CD86 (see Banchereau et al., Nature 392:245 (1998)). During the maturation process, DCs migrate to the T lymphocyte areas of draining lymph nodes. After exposure to inflammatory stimuli, DCs mature, lose their antigen processing capacity, display increased levels of costimulatory molecules and secrete increased amounts of cytokines and chemokines that aid T cell activation. In addition to their role in inducing immunity to foreign antigens, DCs are involved in inducing tolerance to self-antigens. Recent studies have shown a correlation between the presence of DCs with a semi-mature DC phenotype and the ability to tolerize lymph node T cells against tissue-derived self-antigens. Lutz, M. B., et al., Trends Immunol. 23 (9):445-449 (2002); Steinman R. M. et al., Annu. Rev. Immunol. 21:685-711 (2003).
DCs express surface receptors that recognize pathogen-associated molecule patterns, such as bacterial LPS, unmethylated CpG motifs of bacterial DNA, and double-stranded viral RNA (see Underhill, D., et al., Curr. Opin. Immunol. 14:103 (2002)). Antigen receptors expressed by DCs include members of the C-type lectin family, which bind sugars in a calcium-dependent manner using highly conserved carbohydrate recognition domains (CRDs). Recently, C-type lectin-like receptors have been characterized which consist of a CRD-like domain that may bind protein or lipids rather than carbohydrates (Kogelberg, H., et al., Curr. Opin. Struct. Biol. 11:635 (2001); Cambi A. et al., Curr. Opin. Cell Biol. 15(5):539-546 (2003)).
Given the important role DCs play in immune regulation, there is a need for agents that modulate the ability of DCs to stimulate the immune response. It has now been discovered that a novel dendritic cell-associated C-type Lectin-like molecule (DCAL-1) type II acts as a costimulatory molecule to enhance IL-4 production by CD4+ T cells and also plays a role in DC maturation.